Solid forms of Ivacaftor and processes for the preparation thereof

Abstract

Provided herein is a polymorphic form of Ivacaftor, namely APO-I, as well as processes for the preparation and pharmaceutical compositions of the same. Also, provided is a new solvate of Ivacaftor, processes for its preparation and use in the preparation of pure Ivacaftor.

What is claimed is: 
     
       1. A polymorphic form APO-I of Ivacaftor having a powder x-ray diffractogram comprising peaks, in terms of 2-theta degrees, at: 4.3±0.2, 4.8±0.2, 9.5±0.2, 13.0±0.2, 20.0±0.2 and 28.8±0.2. 
     
     
       2. The polymorphic form APO-I of Ivacaftor of  claim 1 , wherein the powder x-ray diffractogram further comprises at least one peak, in terms of 2-theta degrees, selected from the group consisting of: 9.0±0.2, 12.0±0.2, 14.8±0.2, 16.1±0.2, 21.7±0.2 and 27.9±0.2. 
     
     
       3. The polymorphic form APO-I of Ivacaftor of  claim 1 , having a DSC thermogram having endothermic peaks at about 240.8° C. and about 315.8° C. and an exothermic peak at about 245.9° C. 
     
     
       4. A process for the preparation of a polymorphic form APO-I of Ivacaftor of  claim 1 , wherein the process comprises the following steps:
 (a) adding an Ivacaftor solvate to an organic solvent or a mixture of organic solvents selected from the group consisting of methanol, ethanol, propanol, isopropanol, butanol, toluene, xylene, hexane and heptane, thereby forming a reaction mixture; 
 (b) maintaining the reaction mixture at a temperature range of from about 0° C. to about 30° C.; and 
 (c) isolating the polymorphic form APO-I of Ivacaftor. 
 
     
     
       5. The process of  claim 4 , wherein the Ivacaftor solvate is a solvate with methanol, ethanol, methyl ethyl ketone, isopropyl acetate, acetonitrile, methyl isobutyl ketone or water. 
     
     
       6. The process of  claim 4 , wherein the Ivacaftor solvate is a methyl isobutyl ketone solvate of Ivacaftor. 
     
     
       7. The process of  claim 4 , wherein the organic solvent is methanol, ethanol, propanol, isopropanol, butanol, toluene, xylene, hexane, heptane or a mixture thereof. 
     
     
       8. The process of  claim 7 , wherein the organic solvent is a mixture of toluene and methanol and wherein the volume ratio of toluene to methanol in the mixture is in the range of from about 1 to 1 to about 1 to 10. 
     
     
       9. A pharmaceutical composition comprising the polymorphic form APO-I of Ivacaftor of  claim 1  with one or more pharmaceutically acceptable carriers.